PROGNOSTIC RELEVANCE OF THE GENE EXPRESSION SIGNATURE IN PRIMARY AND SECONDARY MYELOFIBROSIS
Author(s): ,
Sebastiano Rontauroli
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
,
Roberta Zini
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
,
Elisa Bianchi
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
,
Elena Genovese
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
,
Chiara Carretta
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
,
Sandra Parenti
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
,
Sebastian Fantini
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
,
Selene Mallia
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
,
Sara Castellano
Affiliations:
Center for Genome Research,University of Modena and Reggio Emilia,Modena,Italy
,
Paola Guglielmelli
Affiliations:
CRIMM, Center for Research and Innovation for Myeloproliferative Neoplasms,AOU Careggi, and Dept of Experimental and Clinical Medicine, Univ. of Florence,Florence,Italy
,
Daniela Pietra
Affiliations:
Department of Hematology Oncology,IRCCS Policlinico San Matteo Foundation and University of Pavia,Pavia,Italy
,
Elisa Rumi
Affiliations:
Department of Hematology Oncology,IRCCS Policlinico San Matteo Foundation and University of Pavia,Pavia,Italy
,
Silvia Salmoiraghi
Affiliations:
Hematology,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Federica Delaini
Affiliations:
Hematology,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Barbara Mora
Affiliations:
Division of Hematology,Ospedale ASST Sette Laghi, Universita degli Studi dell'Insubria,Varese,Italy
,
Lorenzo Elli
Affiliations:
SSD Laboratorio Analisi - SMEL Specializzato in Citogenetica e Genetica Medica,ASST Settelaghi, Ospedale di circolo, Fondazione Macchi,Varese,Italy
,
Raffaella Accetta
Affiliations:
SSD Laboratorio Analisi - SMEL Specializzato in Citogenetica e Genetica Medica,ASST Settelaghi, Ospedale di circolo, Fondazione Macchi,Varese,Italy
,
Laura Villani
Affiliations:
Center for the Study of Myelofibrosis,Foundation IRCCS Policlinico San Matteo,Pavia,Italy
,
Cristina Azzan
Affiliations:
Center for the Study of Myelofibrosis,Foundation IRCCS Policlinico San Matteo,Pavia,Italy
,
Vittorio Rosti
Affiliations:
Center for the Study of Myelofibrosis,Foundation IRCCS Policlinico San Matteo,Pavia,Italy
,
Francesco Passamonti
Affiliations:
Division of Hematology,Ospedale ASST Sette Laghi, Universita degli Studi dell'Insubria,Varese,Italy
,
Alessandro Rambaldi
Affiliations:
Hematology,ASST Papa Giovanni XXIII,Bergamo,Italy
,
Mario Cazzola
Affiliations:
Department of Hematology Oncology,IRCCS Policlinico San Matteo Foundation and University of Pavia,Pavia,Italy
,
Alessandro M. Vannucchi
Affiliations:
CRIMM, Center for Research and Innovation for Myeloproliferative Neoplasms,AOU Careggi, and Dept of Experimental and Clinical Medicine, Univ. of Florence,Florence,Italy
,
Enrico Tagliafico
Affiliations:
Center for Genome Research,University of Modena and Reggio Emilia,Modena,Italy
Rossella Manfredini
Affiliations:
Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences,University of Modena and Reggio Emilia,Modena,Italy
EHA Library. Rontauroli S. Jun 14, 2019; 266454; PF655
Dr. Sebastiano Rontauroli
Dr. Sebastiano Rontauroli
Contributions
×
Abstract

Abstract: PF655

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Primary myelofibrosis (PMF) together with polycythemia vera (PV) and essential thrombocythemia (ET) belongs to the classic Philadelphia-negative myeloproliferative neoplasms (MPNs). PV and ET can evolve to secondary myelofibrosis (SMF) giving rise to post-PV (PPV) and post-ET (PET) myelofibrosis (MF). PMF and SMF patients are currently managed in the same way and prediction of survival is based on the same prognostic models, even if it has been demonstrated that they can’t accurately distinguish different risk categories in SMF. In the last few years interest grew concerning the ability of gene expression profiling (GEP) to provide valuable prognostic information for clinical decision making. Several studies demonstrated that GEP can improve risk classification in hematologic malignancies such as AML, MDS and lymphoma. 

Aims
As a preliminary result we performed GEP in PMF and SMF CD34+ cells and identified a gene signature that was able to distinguish patients with a better prognosis from that with a worse one. To confirm these results and to ease the possible clinical use of a molecular signature based on gene expression we decided to move to a more accessible cell population.

Methods
Granulocytes were isolated from 114 MF patients (35 prefibrotic/early PMF, 37 overt PMF, 26 PET and 16 PPV) and total cellular RNA was extracted. Gene expression profiling (GEP) was performed using Affymetrix platform. In order to identify genes whose expression is related to survival in MF patients, we performed a Cox regression analysis by means of Partek GS Software.

Results

Cox regression analysis led to the identification of a list of 650 transcripts which discriminate high-risk (HR) MF patients from low-risk (LR) ones. According to our results, the frequency of deceased patients was increased in the HR group and survival curves demonstrated that the median overall survival was lower in the HR group compared to the LR one (3.25 y vs 6.88 y, Log-rank p-value < 0.01). Moreover, we observed that 11 out of 13 AML transformed patients clustered within the HR group. Interestingly, we found that HR group was enriched in patients carrying at least one high molecular risk mutation (EZH2, ASXL1, IDH1/2, SRSF2), while there was no significant difference between the two groups regarding the disease and the driver mutation. Concerning clinical variables, we observed that median age at diagnosis was higher in the HR group (65.6 y vs 62.1 y, p-value < 0.05). WBC count was increased in the HR group (12.9 x109/L vs 9.3 x109/L, p-value < 0.05), while platelet count was decreased in the same group compared to LR ones (218 x109/L vs 352 x109/L, p-value < 0.01). Moreover, the percentage of patients with more than 1% circulating blasts is greater in the HR group. Finally, we studied the distribution of samples classified according to DIPSS prognostic model. Strikingly, our gene signature classifies as HR several patients belonging to the DIPSS low and intermediate-1 categories. These patients are deceased or leukemia transformed into a shorter time frame than the median survival reported for the reference prognostic class.

Conclusion
Our results demonstrate that GEP of primary MF cells colud be a useful tool for risk prediction in PMF and SMF since it can improve the identification of patients’ subgroups characterized by a poor prognosis. These results should be validated in independent patient cohorts in order to confirm their predictive power.

Session topic: 15. Myeloproliferative neoplasms - Biology & Translational Research

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies